Molecular cloning and characterization of two novel human renal organic anion transporters (hOAT1 and hOAT3)

被引:125
作者
Race, JE
Grassl, SM
Williams, WJ
Holtzman, EJ
机构
[1] SUNY Hlth Sci Ctr, Dept Med, Syracuse, NY 13210 USA
[2] SUNY Hlth Sci Ctr, Dept Pharmacol, Syracuse, NY 13210 USA
[3] SUNY Hlth Sci Ctr, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA
关键词
kidney; organic anion transport; p-aminohippurate; homology cloning;
D O I
10.1006/bbrc.1998.9978
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The cloned organic anion transporters from rat, mouse, and winter flounder (rOAT1, mOAT1, fROAT) mediate the coupled exchange of alpha-ketoglutarate with multiple organic anions, including p-aminohippurate (PAH). We have isolated two novel gene products from human kidney which bear significant homology to the known OATs and belong to the amphiphilic solute facilitator (ASF) family. The cDNAs, hOAT1 and hOAT3, encode for 550- and 568-amino-acid residue proteins, respectively. hOAT1 and hOAT3 mRNAs are expressed strongly in kidney and weakly in brain. Both genes map to chromosome 11 region q11.7. PAH uptake by Xenopus laevis oocytes injected with hOAT1 mRNA is increased 100-fold compared to water-injected oocytes. PAH uptake is chloride dependent and is not further increased by preincubation of oocytes in 5 mM glutarate. Uptake of PAH is inhibited by probenicid, alpha-ketoglutarate, bumetanide, furosemide, and losartan, but not by salicylate, urate, choline, amilioride, and hydrochlorothiazide. (C) 1999 Academic Press.
引用
收藏
页码:508 / 514
页数:7
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